tac-101 in treating patients with advanced hepatocellular carcinoma (liver cancer)

Conditions: Liver Cancer

Summary: rationale: tac-101 may stop the growth of cancer by stopping blood flow to the tumor. purpose: this phase i/ii trial is studying the side effects and best dose of tac-101 and to see how well it works in treating patients with advanced hepatocellular carcinoma (liver cancer).

objectives: phase i * primary * determine the maximum tolerated dose (mtd) of tac-101 in patients with advanced hepatocellular carcinoma. * determine the safety of 2 consecutive courses of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. * determine the toxic and adverse effects profile of this drug in these patients. phase ii * primary * determine the objective antitumor response rate in patients treated with this drug at the mtd. * secondary * determine the overall survival time of patients treated with this drug. * determine the time to disease progression in patients treated with this drug. * determine the duration of observed objective response, using who criteria and measurements of serum alpha-fetoprotein concentrations, in patients treated with this drug. * determine the time to treatment failure in patients treated with this drug. * determine the safety and tolerability of intermittent treatment with this drug in these patients. outline: this is an open-label, dose-escalation study. * phase i: patients receive oral tac-101 once daily on days 1-14. treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. cohorts of 6 patients receive escalating doses of tac-101 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. * phase ii: patients receive oral tac-101 at the mtd (determined in phase i) once daily on days 1-14. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. patients are followed at 35-60 days. projected accrual: a total of 6-18 patients for the phase i portion and 21-41 patients for the phase ii portion will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed hepatocellular carcinoma * at least 1 previously unirradiated, bidimensionally measurable lesion greater than 20 mm by mri or conventional ct scan or at least 10 mm by spiral ct scan * patients with cns involvement must have completed appropriate treatment and have no progressive neurologic deficits within the past 28 days * no carcinomatous meningitis patient characteristics: age * 18 to 80 performance status * ecog 0-2 life expectancy * more than 12 weeks hematopoietic * hemoglobin ≥ 10.0 g/dl * wbc ≥ 2,000/mm\^3 * absolute neutrophil count ≥ 1,000/mm\^3 * platelet count ≥ 40,000/mm\^3 * no abnormal bleeding or clotting hepatic * no grade c child-pugh cirrhosis * ast and alt ≤ 2.5 times upper limit of normal (uln) * albumin ≥ 2.8 g/dl * inr ≤ 1.5 times uln * bilirubin ≤ 2.0 mg/dl renal * creatinine ≤ 1.5 times uln cardiovascular * no prior deep vein thrombosis * no prior superficial venous thrombosis * no family history of thromboembolism in a first-degree relative * no lower extremity thromboses by doppler ultrasound (unless a subsequent venous angiography confirms a false positive ultrasound) pulmonary * no prior pulmonary embolism other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception, except oral contraceptives containing estrogen * fasting triglycerides ≤ 400 mg/dl for men or ≤ 325 mg/dl for women * no other malignancy within the past 3 years except inactive nonmelanoma skin cancer or carcinoma in situ of the cervix * no uncontrolled metabolic disorders, other nonmalignant organ or systemic disease, or secondary effects of cancer that induce a high medical risk * no known allergy or hypersensitivity to tac-101 or its components prior concurrent therapy: biologic therapy * no prior thalidomide * no prior putative antiangiogenesis therapy * prior interferon allowed chemotherapy * no more than 2 prior chemotherapy regimens endocrine therapy * no concurrent estrogen products radiotherapy * see disease characteristics * more than 21 days since prior radiotherapy, except small portal radiotherapy used for the palliation of isolated, symptomatic, osseous metastases * no prior radiotherapy to evaluable lesions * no concurrent radiotherapy unless for bone pain that is present before beginning study surgery * not specified other * prior anticancer treatment allowed provided there is clear evidence of progressive disease after the most recent treatment * more than 21 days since prior anticancer therapy and recovered * no more than 2 prior treatment regimens * no concurrent therapeutic anticoagulants * concurrent low-dose warfarin for prophylactic care of indwelling venous access devices allowed * no concurrent azoles or tetracyclines * no concurrent medications known or suspected to increase risk of venous thromboembolism * no other concurrent retinoids

Keywords: advanced adult primary liver cancer recurrent adult primary liver cancer adult primary hepatocellular carcinoma localized unresectable adult primary liver cancer oral tac-101